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Atomoxetine to Treat Asian Adult Patients With Attention-Deficit/Hyperactivity Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00962104
First received: August 18, 2009
Last updated: August 10, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to assess the efficacy, the quality of life, and the safety of multiple dosing atomoxetine in Asian adult subjects with attention deficit/hyperactivity disorder (ADHD).


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
Drug: Atomoxetine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Placebo-Controlled Asian Study of Atomoxetine Hydrochloride in the Treatment of Adult Patients With Attention-Deficit/Hyperactivity Disorder (ADHD)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    CAARS-Inv:SV is a scale that assesses symptom severity over past week. Total ADHD symptom score consisted of 18 items (sum of inattention [9 items, range: 0-27] and hyperactivity-impulsivity [9 items, range: 0-27] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently) for total score range of 0 to 54. Higher scores indicate greater impairment.


Secondary Outcome Measures:
  • Change From Baseline in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life-29 (AAQoL) Scores up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    Participant-reported outcome measure used to examine disease-specific functional impairments and QoL for adults with ADHD. The domains include work functioning, family relationships, social functioning, activities of daily living (that is, driving, managing finances), and psychological adaptation (that is, life satisfaction and self-esteem). Individual items scored on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). Range of scores for this subscale is 0 to 100. Consistent with the majority of existing QoL measures, higher scores on AAQoL-29 indicate better functioning.

  • Change From Baseline in the European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state.

  • The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    CAARS-Inv:SV assesses symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention [9 items, range: 0-27] and hyperactivity-impulsivity [9 items, range: 0-27] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment*visit. Baseline included as a covariate; thus, treatment difference in observed value is same as change from baseline.

  • The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Screening Version (CAARS-S:SV) 18 Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Participant assessment of symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention [9 items, range: 0-27] and hyperactivity-impulsivity [9 items, range: 0-27] subscales) using 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment*visit. Baseline included as covariate; thus, treatment difference in observed value is same as change from baseline.

  • Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    A 75-item standardized self-reported measure comprised of 3 subscales. Each item is rated on a 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75- 225 total score). Higher subscale ratings=greater perceived impairment.

  • Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    Third-party observer of participant completes 75-item scale. Comprised of 3 subscales. Each item rated on 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75-225 total score). Higher subscale ratings=greater perceived impairment.

  • Change From Baseline in the Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    The CGI-ADHD-S is a single-item clinician rating of the clinician's assessment of the overall severity of the participant's ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill to 7=among the most extremely ill participants).

  • Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) up to 10 Weeks [ Time Frame: Up to 10 weeks ] [ Designated as safety issue: No ]
    The CGI-ADHD-I is a single-item clinician rating of the clinician's assessment of the participant's improvement in ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment (1=very much improved to 7=very much worsened).

  • Change From Baseline in the Hamilton Anxiety Rating Scale-14 Items (HAMA-14) up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    Clinician-administered rating scale that assesses severity of anxiety and its improvement (or change) during course of treatment (Hamilton 1959; Riskind et al. 1987). Scale consists of 14 items that provide an overall measure of general anxiety, including psychic anxiety and somatic anxiety. Investigator talked to participant about participant's symptoms over previous week before study visit. Each item is rated on a 5-point scale of 0 (absent) to 4 (very severe). Total score=sum of 14 items and ranges from 0 (normal) to 56 (severe). Higher scores indicate a greater degree of symptom severity.

  • Change From Baseline in the Hamilton Depression Rating Scale-17 Items (HAMD-17 Total) up to 10 Weeks [ Time Frame: Baseline, up to 10 weeks ] [ Designated as safety issue: No ]
    The HAMD-17 was used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present) to 4 (very severe) or a 3-point scale of 0 (not present) to 2 (marked). Higher scores indicate greater symptom severity. The total score is the sum of the scores from HAMD-17 Items 1 through 17. The total score may range from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate a greater degree of symptom severity.


Enrollment: 391
Study Start Date: August 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atomoxetine Drug: Atomoxetine
40-120 milligrams (mg) taken by mouth, once daily for 10 weeks.
Other Name: LY139603
Placebo Comparator: Placebo Drug: Placebo
Taken by mouth, once daily for 10 weeks.

Detailed Description:

The treatment will be initiated at the lowest dosage 40 milligrams per day (mg/day), and it will be titrated up to 80 mg/day. Patients who are unable to tolerate a dose of at least 80 mg/day through the end of this study will be discontinued. The dosage will be titrated up to a maximum of 120 mg/day.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for current attention deficit/hyperactivity disorder (ADHD) as well as criteria for a historical diagnosis of ADHD during childhood, both assessed by the Conners' Adult Attention-Deficit/Hyperactivity Disorder Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition at screening
  • Patients must have a score of 2 or greater on at least 6 items of either the inattentive or hyperactive/impulsive core subscales at randomization or screening on the rated Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-item total ADHD symptom score. In addition, their total score on the 18-item total ADHD symptom score must be 20 or greater.
  • Patients must have a Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity score of 4 (moderate symptoms) or greater.
  • Patients must have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, required by the protocol.
  • Patients must possess an educational level and degree of understanding of the language of their country that enables them to communicate suitably with the investigator and study coordinator.
  • Patients must be able to swallow capsules.

Exclusion Criteria:

  • Patients who meet full DSM-IV-TR diagnostic criteria for any history of bipolar disorder or any history of schizophrenia and other psychotic disorders, or patients who had received injectable sustained-release neuroleptics.
  • Patients with depressive disorder who also have a total score of 12 or greater on the Hamilton Depression Rating Scale-17 items at randomization. Patients who have both a current or past history of major depression and received any anti-depression drug therapy within 6 months of screening.
  • Patients who meet DSM-IV-TR diagnostic criteria for current anxiety disorder and also patients who require anti-anxiety drug therapy, except for those taking benzodiazepine analogs for anxiety, which need to be limited.
  • Patients who have been diagnosed (DSM-IV-TR) with a pervasive developmental disorder.
  • Patients who, in the opinion of the investigator, are at serious suicidal risk or serious risk of harming others, or whose score for Item 11 on the Hamilton Depression Rating Scale-17 items is equal or more than 2 at randomization or screening.
  • Patients who have received atomoxetine in a prior clinical study.
  • Patients with significant medical conditions that are likely to become unstable during the trial or would likely be destabilized by treatment with atomoxetine.
  • Patients with a history of allergy to atomoxetine, severe allergies to more than 1 class of medications, or multiple adverse drug reactions.
  • Patients who have received treatment within the past 30 days with a drug that has not received regulatory approval for any indication at the time the informed consent document is obtained.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00962104

Locations
Japan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Aichi, Japan, 466-8560
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Chiba, Japan, 260-0842
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Fukushima, Japan, 960-1295
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Hokkaido, Japan, 060-0814
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Hyogo, Japan, 661-0002
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Kanagawa, Japan, 231-0023
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Kumamoto, Japan, 862-0920
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Kyoto, Japan, 606-8397
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Nara, Japan, 634-8522
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Osaka, Japan, 590-0947
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Saitama, Japan, 350-0495
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Tokyo, Japan, 160-0023
Korea, Republic of
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Bucheon, Korea, Republic of, 420-767
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Gwangjin-Gu, Korea, Republic of, 143-711
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Jeonju-Si, Korea, Republic of, 561712
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Seoul, Korea, Republic of, 120-752
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Sungnam-Si, Korea, Republic of, 463-712
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Yangsan, Korea, Republic of, 626-770
Taiwan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Keelung, Taiwan, 204
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Neihu Taipei, Taiwan, 114
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Niao Sung Hsiang, Taiwan, 83301
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Taichung City, Taiwan, 40201
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Taipei, Taiwan, 100
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tao-Yuan, Taiwan, 333
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Publications:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00962104     History of Changes
Other Study ID Numbers: 12107, B4Z-JE-LYEE
Study First Received: August 18, 2009
Results First Received: February 6, 2012
Last Updated: August 10, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eli Lilly and Company:
ADHD

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Dyskinesias
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Atomoxetine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014